A DNA chip, a protein chip, and the like are currently used as useful tools for comprehensively analyzing biomolecules. In the case of these chips, DNAs or proteins are immobilized on a substrate in an array form, and they are then subjected to an appropriate reaction system that depends on purposes, so as to comprehensively identify molecules that are likely to exhibit functions of interest.
With regard to such DNA chip, at present, the method of Affymetrix, Inc., which comprises synthesizing DNA on a chip using an optical lithography technique and then matching location information and sequence information, and the method of Stanford University, which comprises attaching DNA whose sequence has been known to a chip, are widely used. In order to examine a large number of sequences at once, the Affymetrix method is advantageous. In order to examine a limited number of DNAs whose sequences have been known, the Stanford method is convenient. Thus, the two types of methods are used, depending on purposes.
On the other hand, with regard to production of a protein chip, Phylos, Inc. has attempted to hybridize the mRNA region of IVV (in vitro virus) with an Affymetrix-type DNA substrate, so as to assign numbers to proteins on a chip and to non-covalently immobilize them thereon (Non-Patent Document 1). However, a majority of protein chips are produced by the Stanford method of producing such protein chips by spotting a limited number of specific proteins. Hence, under the present circumstances, it is extremely difficult to produce protein chips from an enormous library comprising genes having unknown sequences. In this respect, the method of Phylos, Inc. is most advantageous. However, since hybridization is used in immobilization of proteins in the method of Phylos, Inc., this method is not considered as a stable immobilization method, when an enzyme assay is carried out under various buffer conditions. Thus, this method has not yet been practically used. In addition, since this method comprises a process of introducing a region to be hybridized as a tag, it is not necessarily said that it is efficient from the viewpoint of practical utility.
The present inventors have provided various techniques for identification and development of useful proteins using the IVV (in vitro virus) method (Patent Document 1). The IVV method has attracted attention as a method of selecting a peptide molecule of interest from large quantities of peptides having random sequences or a peptide library comprising such peptides, which is advantageous in terms of evolutionary engineering. The IVV method is capable of matching nucleic acid sequence information and the activity or function of the corresponding protein on a one-to-one basis. Thus, if this method could be used in a comprehensive analysis, proteins with desired activity and information regarding nucleic acid sequences encoding the same can be obtained simultaneously in a large volume. However, at the present stage, techniques of applying such method to comprehensive analyses have not yet been reported.    [Non-Patent Document 1] Weng et al., Proteomics. 2: 48-57, 2002    [Patent Document 1] International Publication WO2006/041194